Molecular basis for disassembly of an importin:ribosomal protein complex by the escortin Tsr2
| Autor: | Schütz, Sabina, Michel, Erich, Damberger, Fred F, Oplová, Michaela, Peña, Cohue, Leitner, Alexander, Aebersold, Ruedi, Allain, Frederic H-T, Panse, Vikram Govind |
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| Přispěvatelé: | University of Zurich, Panse, Vikram Govind |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Ribosomal Proteins
Cytoplasm Magnetic Resonance Spectroscopy animal structures Protein Conformation Science Active Transport Cell Nucleus 610 Medicine & health 1600 General Chemistry Saccharomyces cerevisiae Karyopherins environment and public health Article Mass Spectrometry 1300 General Biochemistry Genetics and Molecular Biology Humans lcsh:Science In Situ Hybridization Fluorescence Cell Nucleus 10179 Institute of Medical Microbiology Circular Dichroism Nuclear Proteins 3100 General Physics and Astronomy Recombinant Proteins Hematopoiesis Phenotype ran GTP-Binding Protein Mutation embryonic structures 570 Life sciences biology RNA lcsh:Q Apoptosis Regulatory Proteins Ribosomes Allosteric Site Protein Binding |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-06160-x |
| Popis: | Disordered extensions at the termini and short internal insertions distinguish eukaryotic ribosomal proteins (r-proteins) from their anucleated archaeal counterparts. Here, we report an NMR structure of such a eukaryotic-specific segment (ESS) in the r-protein eS26 in complex with the escortin Tsr2. The structure reveals how ESS attracts Tsr2 specifically to importin:eS26 complexes entering the nucleus in order to trigger non-canonical RanGTP-independent disassembly. Tsr2 then sequesters the released eS26 and prevents rebinding to the importin, providing an alternative allosteric mechanism to terminate the process of nuclear import. Notably, a Diamond–Blackfan anemia-associated Tsr2 mutant protein is impaired in binding to ESS, unveiling a critical role for this interaction in human hematopoiesis. We propose that eS26-ESS and Tsr2 are components of a nuclear sorting system that co-evolved with the emergence of the nucleocytoplasmic barrier and transport carriers. Ribosomal proteins are transported to the nucleus with the help of importins, from which they are released prior to incorporation into the nascent ribosome. Here the authors report the NMR structure of the ribosomal protein eS26 in complex with the escortin Tsr2 and shed light on the mechanism of eS26 release from importin. |
| Databáze: | OpenAIRE |
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